This invention relates to a process for resolution of racemic 5-phenyl-2-pentanol to (S)-5-phenyl-2-pentanol, a valuable intermediate in the synthesis of analgesic agents. More specifically, the process comprises esterifying racemic 5-phenyl-2-pentanol to form the hemiphthalate ester, followed by treating said ester with (+)-brucine, separating (S)-5-phenyl-2-pentylbrucine hemiphthalate salt, decomposing said salt to regenerate (S)-5-phenyl-2-pentylhemiphthalate, and hydrolyzing said ester to (S)-5-phenyl-2-pentanol.
The resolution of alcohols by converting them to hemiphthalate esters followed by diastereomer salt formation of said esters with an optically active base is described by Wilen in "Topics in Stereochemistry," edited by Allinger and Eliel, Wiley-Interscience, N.Y., Vol. 6, page 141 (1971).
The preparation of racemic 5-phenyl-2-pentanol by the reaction of 3-phenylpropylmagnesium bromide with acetaldehyde is reported by Roblin et al., J. Am. Chem. Soc. 57, 151-159 (1935).
It is a valuable intermediate for the synthesis of d1-5,6,6a-beta,7,8,9-alpha,10,10a-alpha-octahydro-1-acetoxy-9-hydroxy-6-be ta-methyl-3-(1-alpha-methyl-4-phenylbutoxy)benzo[c]quinoline, an analgesic agent. The preparation of said compound and its use as an analgesic are described in U.S. Pat. No. 4,260,764, issued Apr. 7, 1981.